U.S. Pat. No. 5,010,090 (assigned to Novo Nordisk, referred to hereinafter as '090) discloses tiagabine hydrochloride and the process of its preparation. The process adopted herein is very laborious and expensive as it utilizes column chromatography for purification. Further, the product is crystallised using ethyl acetate, isopropanol, acetone or water yielding product contaminated with high levels of solvent. Use of alternative organic solvents such as acetonitrile, butylacetate, toluene, acetone, dichloromethane etc. also gives product containing various amounts of the used crystallization solvent. The crystallization solvents are unwanted as they affect the stability of pharmaceutical products and are toxic to humans. Further the product manufactured using ethylacetate and other organic solvents often forms clathrates, hence not usable as pharmaceutical material due to high levels of solvent contamination. This patent does not disclose the polymorphic form of tiagabine hydrochloride.
U.S. Pat. No. 5,354,760 (assigned to Novo Nordisk, referred to hereinafter as '760) patent provides monohydrate form of tiagabine hydrochlrodie referred to herein as form I. The monohydrate form of tiagabine hydrochloride is stable, non-hygroscopic and is suitable for pharmaceutical formulations as the only residual solvent in the product is water. However, it is reported that the monohydrate crystalline form is less stable at elevated temperature making its use inconvenient during formulation. The '760 patent discloses a process of preparation of form I tiagabine hydrochloride (monohydrate) comprising crystallization of tiagabine hydrochloride form an aqueous solution.
U.S. Pat. No. 5,958,951 (assigned to Novo Nordisk, referred to hereinafter as '951) claims anhydrous crystalline form of tiagabine hydrochloride referred to herein as form II. The product obtained was reported to be non-hygroscopic and thermally stable. The process for preparation of form II claimed in '951 was the same as the process disclosed in '760, however the examples differ with respect to the conditions of crystallization for example in the exemplified process of '951 the crystallization from aqueous solution may occur at high temperature of about 52° C. over a period of about 18 hours. Thus, the process for the preparation of anhydrous form is time consuming.